Measurement levels of norepinephrine (NE) and its metabolites in plasma, urine, and cerebrospinal fluid have been developed and are being applied to studies of changes of these metabolites in patients with various disorders of the autonomic nervous system and in rats after administration of drugs which alter synthesis, storage, release, metabolism, or uptake of NE in sympathetic nerves. Consistent with metabolism of NE by monoamine oxidase after neuronal uptake, drugs such as desipramine (or cocaine) which block uptake, enhance apparent release of norepinephrine into the circulation and diminish formation of its deaminated metabolites DHPG and MHPG. Other studies focus on the regulation of release by peptides such as Vasoactive Intestinal Peptide and Atrial Natriuretic Factors. These studies are carried out in pithed rats. The relationship between plasma NE levels and concentrations at the neuroeffector junction are determined by measurements of NE in plasma during NE infusion or NE release from sympathetic neurones in relation to responses. This method, developed in pithed rats is being applied to studies in human forearm. In the course of such studies, venous-arterial differences in L-DOPA have been found and it appears that L-DOPA is formed in the sympathetic neurones and overflows into the blood.